Poloxamers are nonionic triblock copolymers composed of a central hydrophobic chain of polyoxypropylene (poly(propylene oxide)) flanked by two hydrophilic chains of polyoxyethylene (poly(ethylene oxide)). Poloxamers are often considered “functional excipients” because they are essential components and play an important role in a formulation.
Poloxamers are synthetic triblock co-polymers with the following general structure formula:
wherein a=2-130 and b=15-67
Non-limiting examples of poloxamers include: poloxamer 124, poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 237, poloxamer 338, and poloxamer 407. The chemical characteristics of each poloxamer are determined by the chain length of the polyethylene (EO) units and the polyoxypropylene (PO) units, molecular weight and degree of hydrophobicity/hydrophilicity. Some poloxamers are liquid at room temperature (124) whereas others are a solid (184, 185, 188, 237, 338, and 407). Poloxamers have a variety of uses including as emulsifying agents, solubilizing agents and stabilizing agents. For example, poloxamer 188 has been used as an emulsifying agent for fluorocarbons used as artificial blood substitutes and in the preparation of solid-dispersions. They are also used as wetting agents in ointments, suppository bases, and gels, as well as tablet binders and coatings. In some cases, poloxamers have been used for solubilizing formulations containing otic therapeutic agents and their delivering. In some cases, a poloxamer formulation is created containing active agents that is liquid when at 4° C. which gels when heated at or above room temperature. This enables the formulation to be injected through a small needle and gel when it hits the middle ear. In these cases the amounts of poloxamer used for solubilization was about 15-17 wt %. At concentrations above 15-17 wt %, poloxamers will typically form gels that are not flowable even with cooled to 4° C., making them unsuitable for injection. There is a need for injectable formulations of therapeutic agents containing a poloxamer with gelation temperatures of at least 10 degrees or at least body temperature, where the poloxamer is at concentrations higher than about 15-17 wt %.